Efficacy and Safety of Dichlorphenamide for Primary Periodic Paralysis in Adolescents Compared With Adults

Background: Primary periodic paralyses are rare, hereditary skeletal muscle diseases characterized by episodic muscle weakness. Dichlorphenamide was effective and well tolerated in two studies, including one with adolescents. This analysis describes effects of dichlorphenamide among adolescents and adults. Methods: Patients with primary periodic paralyses in a double-blind, controlled, crossover study were randomized to dichlorphenamide or placebo for nine weeks, with a nine-week or longer between-treatment washout period. Attack rate and severity-weighted attack rate during the final eight weeks of each treatment phase were calculated for adolescents and adults separately. Results: Seven adolescents (10 to <= 17 years) and 66 adults were enrolled; five of seven adolescents were evaluable for efficacy and six for safety. Dichlorphenamide total daily dosing among adolescents was 50 mg (n = 1) or 100 mg (n = 5), and in adults was 105.7 mg (mean; n = 61). In adolescents, the median decrease from baseline in frequency of weekly attacks was greater with dichlorphenamide (-0.96) than with placebo (-0.57), similar to findings in adults (dichlorphenamide, -0.83; placebo, -0.24). Severity-weighted attack frequency was likewise reduced more with dichlorphenamide than with placebo in adolescents and adults. The most common adverse event with dichlorphenamide in adolescents was skin rash (two of six [33%]). In adults, numbness was the most common adverse event (26 of 54 [48%]); skin rash occurred less frequently (10 of 54 [19%]). Conclusions: Dichlorphenamide was comparably effective and tolerated among a small number of adolescents as well as adults, although types of adverse events differed between groups. (C) 2019 The Authors. Published by Elsevier Inc.